BACKGROUND: Interferon-α is a cytokine that has demonstrated activity in patients with supratentorial gliomas, but its ideal dose and schedule of administration is unknown. Studies suggest that low-dose, continuous exposure is more efficacious than intermittent, high doses. The authors performed a phase 2 study of recombinant interferon α-2b with monomethoxy polyethylene glycol (PEG-Intron(®)) in children with diffuse intrinsic pontine glioma (DIPG), a population with dismal survival despite decades of clinical investigation. The primary objective was to compare 2-year survival with a historic cohort that received radiation therapy alone. METHODS: Patients received weekly subcutaneous PEG-Intron(®) at a dose of 0.3 μg/kg beginning 2 to 10 weeks after the completion of radiation therapy until they developed disease progression. Patients were evaluated clinically and radiographically at regular intervals. Serum and urine were assayed for biomarkers before each cycle. Quality-of-life (QOL) evaluations were administered at baseline and before every other cycle of therapy to the parents of patients ages 6 to 18 years. RESULTS: Thirty-two patients (median age, 5.3 years; range, 1.8-14.8 years) were enrolled and received a median of 7 cycles of therapy (range, from 1 cycle to ≥70 cycles). PEG-Intron(®) was well tolerated, and no decrease in QOL scores was noted in the subset of patients tested. The 2-year survival rate was 14%, which was not significantly improved compared with the historic cohort. However, the median time to progression was 7.8 months, which compared favorably with recent trials reporting a time to progression of 5 months in a similar population. CONCLUSIONS: Although low-dose PEG-Intron(®) therapy did not significantly improve 2-year survival in children with DIPG compared with an historic control population, it did delay the time to progression.
BACKGROUND: Interferon-α is a cytokine that has demonstrated activity in patients with supratentorial gliomas, but its ideal dose and schedule of administration is unknown. Studies suggest that low-dose, continuous exposure is more efficacious than intermittent, high doses. The authors performed a phase 2 study of recombinant interferon α-2b with monomethoxy polyethylene glycol (PEG-Intron(®)) in children with diffuse intrinsic pontine glioma (DIPG), a population with dismal survival despite decades of clinical investigation. The primary objective was to compare 2-year survival with a historic cohort that received radiation therapy alone. METHODS:Patients received weekly subcutaneous PEG-Intron(®) at a dose of 0.3 μg/kg beginning 2 to 10 weeks after the completion of radiation therapy until they developed disease progression. Patients were evaluated clinically and radiographically at regular intervals. Serum and urine were assayed for biomarkers before each cycle. Quality-of-life (QOL) evaluations were administered at baseline and before every other cycle of therapy to the parents of patients ages 6 to 18 years. RESULTS: Thirty-two patients (median age, 5.3 years; range, 1.8-14.8 years) were enrolled and received a median of 7 cycles of therapy (range, from 1 cycle to ≥70 cycles). PEG-Intron(®) was well tolerated, and no decrease in QOL scores was noted in the subset of patients tested. The 2-year survival rate was 14%, which was not significantly improved compared with the historic cohort. However, the median time to progression was 7.8 months, which compared favorably with recent trials reporting a time to progression of 5 months in a similar population. CONCLUSIONS: Although low-dose PEG-Intron(®) therapy did not significantly improve 2-year survival in children with DIPG compared with an historic control population, it did delay the time to progression.
Authors: Isabella C Taylor; Marianne Hütt-Cabezas; William D Brandt; Madhuri Kambhampati; Javad Nazarian; Howard T Chang; Katherine E Warren; Charles G Eberhart; Eric H Raabe Journal: J Neuropathol Exp Neurol Date: 2015-08 Impact factor: 3.685
Authors: Kimberly A McDowell; Jacquelyn A Hank; Kenneth B DeSantes; Christian M Capitini; Mario Otto; Paul M Sondel Journal: J Pediatr Hematol Oncol Date: 2015-03 Impact factor: 1.289
Authors: Lindsey M Hoffman; Sophie E M Veldhuijzen van Zanten; Niclas Colditz; Joshua Baugh; Brooklyn Chaney; Marion Hoffmann; Adam Lane; Christine Fuller; Lili Miles; Cynthia Hawkins; Ute Bartels; Eric Bouffet; Stewart Goldman; Sarah Leary; Nicholas K Foreman; Roger Packer; Katherine E Warren; Alberto Broniscer; Mark W Kieran; Jane Minturn; Melanie Comito; Emmett Broxson; Chie-Schin Shih; Soumen Khatua; Murali Chintagumpala; Anne Sophie Carret; Nancy Yanez Escorza; Timothy Hassall; David S Ziegler; Nicholas Gottardo; Hetal Dholaria; Renee Doughman; Martin Benesch; Rachid Drissi; Javad Nazarian; Nada Jabado; Nathalie Boddaert; Pascale Varlet; Géraldine Giraud; David Castel; Stephanie Puget; Chris Jones; Esther Hulleman; Piergiorgio Modena; Marzia Giagnacovo; Manila Antonelli; Torsten Pietsch; Gerrit H Gielen; David T W Jones; Dominik Sturm; Stefan M Pfister; Nicolas U Gerber; Michael A Grotzer; Elke Pfaff; André O von Bueren; Darren Hargrave; Guirish A Solanki; Filip Jadrijevic Cvrlje; Gertjan J L Kaspers; William P Vandertop; Jacques Grill; Simon Bailey; Veronica Biassoni; Maura Massimino; Raphaël Calmon; Esther Sanchez; Brigitte Bison; Monika Warmuth-Metz; James Leach; Blaise Jones; Dannis G van Vuurden; Christof M Kramm; Maryam Fouladi Journal: J Clin Oncol Date: 2018-05-10 Impact factor: 44.544